一例罕见的TCF4基因部分缺失型Pitt-Hopkins综合征的遗传学分析

Genetic analysis of a rare case of Pitt-Hopkins syndrome due to partial deletion of TCF4 gene

目的探讨1例脑发育落后患儿的遗传学病因。方法采用常规G显带技术分析患儿及其双亲的染色体核型,应用单核苷酸多态性微阵列(single nucleotide polymorphism array,SNP-array)技术对患儿进行全基因组拷贝数变异(copy number variations,CNVs)筛查,并对其双亲进行验证。结果患儿及其双亲染色体G显带核型分析均未见异常。SNP-array检测双亲均未见异常,发现患儿染色体18q21.2区存在172 kb(52957042~53129237)的新发缺失,仅涉及OMIM基因TCF4,导致TCF4第6~8外显子的缺失。结论染色体18q21.2区的缺失与Pitt-Hopkins综合征密切相关。SNP-array检测为该患儿的确诊提供了依据。

Objective To explore the genetic basis for a child with delayed intellectual development.Methods The child and his parents were subjected to conventional G-banding karyotyping and single nucleotide polymorphism array(SNP-array)analysis.Suspected copy number variations(CNVs)were verified in both parents.Results No karyotypic abnormality was found with the child and his parents.SNP-array results for both parents were normal.The child was found to harbor a de novo 172 kb deletion at 18q21.2 with a physical position of 52957042-53129237.The deletion only involved one OMIM gene,namely TCF4,resulting in removal of its exons 6 to 8.Conclusion The SNP-array assay has facilitated with the diagnosis of this child.Deletion of 18q21.2 region probably accounts for the Pitt-Hopkins syndrome(PTHS)in this patient.